Estrogens induce expression of membrane-associated estrogen receptor α isoforms in lactotropes

ZARATE S; JAITA G; FERRARIS J; EIJO G; MAGRI ML; PISERA D; SELICOVICH A

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2012 vol. 7 p. 41299 - 41310

1932-6203

Estrogens are key to anterior pituitary function, stimulating hormone release and controlling cell fate to achieve pituitary dynamic adaptation to changing physiological conditions. In addition to their classical mechanism of action through intracellular estrogen receptors (ERs), estrogens exert rapid actions via cell membrane-localized ERs (mERs). We previously showed that E2 exerts a rapid pro-apoptotic action in anterior pituitary cells, especially in lactotropes and somatotropes, through activation of mERs. In the present study, we examined the involvement of mERá in the rapid pro-apoptotic action of estradiol by TUNEL in primary cultures of anterior pituitary cells from ovariectomized rats using a cell-impermeable E2 conjugate (E2-BSA) and an ERá selective antagonist (MPP dihydrochloride). We studied mERá expression during the estrous cycle and its regulation by gonadal steroids in vivo by flow cytometry. We identified ERá variants in the plasma membrane of anterior pituitary cells during the estrous cycle and studied E2 regulation of these mERá variants in vitro by surface biotinylation and Western Blot. E2-BSA-induced apoptosis was abrogated by MPP in total anterior pituitary cells and lactotropes. In cycling rats, we detected a higher number of lactotropes and a lower number of somatotropes expressing mERá at proestrus than at diestrus. Acute E2 treatment increased the percentage of mERá-expressing lactotropes whereas it decreased the percentage of mERá-expressing somatotropes. We detected three mERá isoforms of 66, 39 and 22 kDa. Expression of mERá66 and mERá39 was higher at proestrus than at diestrus, and short-term E2 incubation increased expression of these two mERá variants. Our results indicate that the rapid apoptotic action exerted by E2 in lactotropes depends on mERá, probably full-length ERá and/or a 39 kDa ERá variant. Expression and activation of mERá variants in lactotropes could be one of the mechanisms through which E2 participates in anterior pituitary cell renewal during the estrous cycle.